The pathology of Mycoplasma pneumoniae pulmonary infection for a hamster model was examined after whole bacterium rechallenge or component vaccination. Animals which, after an initial infection, were rechallenged with either live or heat-killed M. pneumoniae inocula developed severe early recall lesions in the first 3 days. In contrast, animals infected once develop maximum histopathology at approximately 10-14 days. A severe perivascular inflammatory cellular infiltrate developed in the rechallenged groups, and pulmonary pathology could also be elicited by rechallenge with bacterial growth medium components. Component vaccination with protein P1 did not reduce disease in comparison to once-infected controls, and vaccination promoted an early immune recall response as well. We conclude that an early immune response needs to be sought in all future experiments of challenge/rechallenge or vaccination. Vaccine studies will require an understanding of both protective and harmful immunogens.